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Mitosis is the key event of the cell cycle during which the sister chromatids are segregated onto two daughter cells. It is well established that abrogation of the normal mitotic progression is a highly efficient concept for anti‐cancer treatment. In fact, various drugs that target microtubules and thus interfere with the function of the mitotic spindle are in clinical use for the treatment of various human malignancies for many years. However, since microtubule inhibitors not only target proliferating cells severe side effects limit their use. Therefore, the identification of novel mitotic drug targets other than microtubules have gained recently much attention. This review will summarize the latest developments on the identification and clinical evaluation of novel mitotic drug targets and will introduce novel concepts for chemotherapy that are based on recent progress in our understanding how mitotic progression is regulated and how anti‐mitotic drugs induce tumor cell death. J. Cell. Biochem. 111: 258–265, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
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Ruiyu Xie Logan J. Everett Hee-Woong Lim Nisha A. Patel Jonathan Schug Evert Kroon Olivia G. Kelly Allen Wang Kevin A. D’Amour Allan J. Robins Kyoung-Jae Won Klaus H. Kaestner Maike Sander 《Cell Stem Cell》2013,12(2):224-237
Highlights? Pancreatic lineage progression is governed by PcG-dependent chromatin remodeling ? A temporal chromatin signature predicts regulators of pancreatic development ? Endocrine cells differentiated from hESCs in vivo are similar to native human islets ? In vitro-produced malfunctioning endocrine cells exhibit aberrant chromatin structure 相似文献
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Morphologically Homogeneous Red Blood Cells Present a Heterogeneous Response to Hormonal Stimulation
Jue Wang Lisa Wagner-Britz Anna Bogdanova Sandra Ruppenthal Kathrina Wiesen Elisabeth Kaiser Qinghai Tian Elmar Krause Ingolf Bernhardt Peter Lipp Stephan E. Philipp Lars Kaestner 《PloS one》2013,8(6)
Red blood cells (RBCs) are among the most intensively studied cells in natural history, elucidating numerous principles and ground-breaking knowledge in cell biology. Morphologically, RBCs are largely homogeneous, and most of the functional studies have been performed on large populations of cells, masking putative cellular variations. We studied human and mouse RBCs by live-cell video imaging, which allowed single cells to be followed over time. In particular we analysed functional responses to hormonal stimulation with lysophosphatidic acid (LPA), a signalling molecule occurring in blood plasma, with the Ca2+ sensor Fluo-4. Additionally, we developed an approach for analysing the Ca2+ responses of RBCs that allowed the quantitative characterization of single-cell signals. In RBCs, the LPA-induced Ca2+ influx showed substantial diversity in both kinetics and amplitude. Also the age-classification was determined for each particular RBC and consecutively analysed. While reticulocytes lack a Ca2+ response to LPA stimulation, old RBCs approaching clearance generated robust LPA-induced signals, which still displayed broad heterogeneity. Observing phospatidylserine exposure as an effector mechanism of intracellular Ca2+ revealed an even increased heterogeneity of RBC responses. The functional diversity of RBCs needs to be taken into account in future studies, which will increasingly require single-cell analysis approaches. The identified heterogeneity in RBC responses is important for the basic understanding of RBC signalling and their contribution to numerous diseases, especially with respect to Ca2+ influx and the associated pro-thrombotic activity. 相似文献
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